Yunfei Li1,2,3, Brock Humphries1,4, Zhishan Wang1,3, Shuyao Lang5, Xuefei Huang5, Hua Xiao1, Yiguo Jiang6, Chengfeng Yang1,3,4,7. 1. Department of Physiology, Michigan State University , East Lansing, Michigan 48824, United States. 2. Department of Pharmaceutics, Institute of Medicinal Biotechnology, Peking Union Medical College , Beijing 100050, People's Republic of China. 3. Department of Toxicology and Cancer Biology and Center for Research on Environmental Disease, College of Medicine, University of Kentucky , Lexington, Kentucky 40536, United States. 4. Cellular and Molecular Biology Graduate Program, Michigan State University , East Lansing, Michigan 48824, United States. 5. Department of Chemistry, Michigan State University , East Lansing, Michigan 48824, United States. 6. Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University , Guangzhou, Guangdong 511436, People's Republic of China. 7. Institute for Integrative Toxicology, Michigan State University , East Lansing, Michigan 48824, United States.
Abstract
Many polycation-based gene delivery vehicles have limited in vivo transfection efficiency because of their excessive exterior positive charges and/or PEGylation, both of which could result in premature dissociation and poor cellular uptake and trafficking. Here, we reported novel hybrid PEGylated nanoparticles (HNPs) that are composed of (a) poly(ethylene glycol)-b-poly(aspartate)-adamantane (PEG-P(asp)-Ad) constituting the outer PEG layer to provide colloidal stability; (b) poly(ethylenimine)10K (PEI10K) forming complex coacervate with P(asp) as the cross-linked cage preventing premature dissociation; (c) cyclodextrin-decorated PEI10K (PEI10K-CD) forming the core with reporter plasmid DNA (pDNA). These HNPs exhibited an increased stability and higher in vitro transfection efficiency compared to traditional PEGylated nanoparticles (PEG-NP). Intratumoral injections further demonstrated that HNPs were able to successfully deliver pDNAs into tumors, while PEG-NP and PEI25K had only negligible delivery efficiencies. Moreover, HNPs' in vivo stability and pDNA delivery capability post intravenous injection were also confirmed by live animal bioluminescence and fluorescence image analysis. It is likely that the coacervation integration at the interface of PEI10K-CD/pDNA core and the PEG shell attributed to the significantly improved in vivo transfection efficiency of HNPs over PEG-NP and PEI25K. This study suggests that the HNP has the potential for in vivo gene delivery applications with significantly improved gene transfection efficiency.
Many polycation-based gene delivery vehicles have limited in vivo transfection efficiency because of their excessive exterior positive charges and/or PEGylationpan>, both of which could result in premature dissociationpan> anpan>d poor cellular uptake anpan>d trafficking. Here, we reported novel hybrid pan> class="Chemical">PEGylated nanoparticles (HNPs) that are composed of (a) poly(ethylene glycol)-b-poly(aspartate)-adamantane (PEG-P(asp)-Ad) constituting the outer PEG layer to provide colloidal stability; (b) poly(ethylenimine)10K (PEI10K) forming complex coacervate with P(asp) as the cross-linked cage preventing premature dissociation; (c) cyclodextrin-decorated PEI10K (PEI10K-CD) forming the core with reporter plasmid DNA (pDNA). These HNPs exhibited an increased stability and higher in vitro transfection efficiency compared to traditional PEGylated nanoparticles (PEG-NP). Intratumoral injections further demonstrated that HNPs were able to successfully deliver pDNAs into tumors, while PEG-NP and PEI25K had only negligible delivery efficiencies. Moreover, HNPs' in vivo stability and pDNA delivery capability post intravenous injection were also confirmed by live animal bioluminescence and fluorescence image analysis. It is likely that the coacervation integration at the interface of PEI10K-CD/pDNA core and the PEG shell attributed to the significantly improved in vivo transfection efficiency of HNPs over PEG-NP and PEI25K. This study suggests that the HNP has the potential for in vivo gene delivery applications with significantly improved gene transfection efficiency.
Entities:
Keywords:
PEGylated; complex coacervation; in vivo delivery; plasmid DNA; transfection efficiency
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